This is more a discussion for the interest checks section, but what the hell, i'll throw an idea or two out. If sci-fi is a main preference, perhaps something with elements found in preexisting role play systems such as Rogue Trader or Cyberpunk would suffice? Something Shadowrun based is another very viable option considering it blends both sci-fi and fantasy pretty well. What would be the goal here as far as characters are concerned? Good, evil, neutral? Will different species be a thing both PC and NPC wise, or will it be human only? Genre wise, what are you looking for beyond sci-fi or fantasy? Combat? Slice of life? Mystery? If we pin these things down first then a plot can be worked around based on what we've got going.